Ethical considerations indicate that the use of radio-labeled drugs should be stringently limited in pre-term or term infants, children and women in potential or actual child-bearing status. Stable isotopically labeled drugs can and have been used in infant studies of bile acid metabolism (Watkins et al., 1973, 1975), alanine and glucose fluxes (Bier et al., 1973) and amino acid metabolism (Curtius et al., 1972). However, the extent of these studies has been limited by the lack of a low-cost instrument for routine analysis, the low sample number through-put and the high labor costs of the only major analytical method: gas chromatography-mass spectroscopy (GC-MS).
Increased clinical applications have been demonstrated for the diagnostic potential of "breath tests" using both radio and stable labeled carbon in diabetes, hepatitis, liver cirrhosis and cystic fibrosis. For example, Helge et al. (1978) showed that diabetic children eliminate .sup.13 CO.sub.2 in their breath at a rate significantly lower than do normal children. The breath test is thus a simple and useful non-invasive procedure for the study of a wide range of metabolism disorders; its general use with clinically preferred .sup.13 C-labeled compounds has, however, been limited because GC-MS has remained the only practical analytical method.
To find a substitute for GC-MS, some effort has been applied to the direct measurement .sup.13 C-labeled carbon dioxide in the presence of .sup.12 C-labeled carbon dioxide under both private and public funds (NIH-NO1-HR-3-3002). Andros Inc. made and patented a fluorescent source infrared gas analyzer in 1973 (U.S. Pat. No. 3,725,701); in 1975, Andros Inc. described (U.S. Pat. No. 4,027,972) a second method of analysis of the level of gaseous .sup.13 -C labeled carbon dioxide through the application of radiant energy to standards in combination with the unknown. Accuracy on the order of five parts per 10.sup.5 was reported; however, the cost of this system was approximately twice that of a suitable GC-MS. This approach is thus at a cost competitive disadvantage to GC-MS and probably does not reduce the sample through-put and labor requirements.